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Generative models, brain function and neuroimaging.

The representational capacity and inherent function of any neuron, neuronal population or cortical area in the brain is dynamic and context-sensitive. Functional integration, or interactions among brain systems, that employ driving (bottom up) and backward (top-down) connections, mediate this adaptive and contextual specialisation. A critical consequence is that neuronal responses, in any given cortical area, can represent different things at different times. This can have fundamental implications for the design of brain imaging experiments and the interpretation of their results. Our arguments are developed under generative models of brain function, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, which are driven by the ensuing error in lower regions, until the mismatch is "cancelled". From this perspective the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because the latter have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for classical models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models may provide incomplete accounts of real brain architectures. Here we focus on the implications for cognitive neuroscience in the context of neuroimaging.

Brain↗

The retrosplenial contribution to human navigation: a review of lesion and neuroimaging findings.

The clinical and neuroimaging literatures are surveyed in order to collate for the first time the available data on retrosplenial involvement in human navigation. Several notable features emerge from consideration of the case reports of relatively pure topographical disorientation in the presence of a retrosplenial lesion. The majority of cases follow damage to the right retrosplenial cortex, with Brodmann's area 30 apparently compromised in most cases. All patients displayed impaired learning of new routes, and defective navigation in familiar environments complaining they could not use preserved landmark recognition to aid orientation. The deficit generally resolved within eight weeks of onset. The majority of functional neuroimaging studies involving navigation or orientation in large-scale space also activate the retrosplenial cortex, usually bilaterally, with good concordance in the locations of the voxel of peak activation across studies, again with Brodmann's area 30 featuring prominently. While there is strong evidence for right medial temporal lobe involvement in navigation, it now seems that the inputs the hippocampus and related structures receive from and convey to right retrosplenial cortex have a similar spatial preference, while the left medial temporal and left retrosplenial cortices seem primarily concerned with more general aspects of episodic memory.

Animals↗

Cognitive processing in literate and illiterate subjects: a review of some recent behavioral and functional neuroimaging data.

The study of illiterate subjects, which for specific socio-cultural reasons did not have the opportunity to acquire basic reading and writing skills, represents one approach to study the interaction between neurobiological and cultural factors in cognitive development and the functional organization of the human brain. In addition the naturally occurring illiteracy may serve as a model for studying the influence of alphabetic orthography on auditory-verbal language. In this paper we have reviewed some recent behavioral and functional neuroimaging data indicating that learning an alphabetic written language modulates the auditory-verbal language system in a non-trivial way and provided support for the hypothesis that the functional architecture of the brain is modulated by literacy. We have also indicated that the effects of literacy and formal schooling is not limited to language related skills but appears to affect also other cognitive domains. In particular, we indicate that formal schooling influences 2D but not 3D visual naming skills. We have also pointed to the importance of using ecologically relevant tasks when comparing literate and illiterate subjects. We also demonstrate the applicability of a network approach in elucidating differences in the functional organization of the brain between groups. The strength of such an approach is the ability to study patterns of interactions between functionally specialized brain regions and the possibility to compare such patterns of brain interactions between groups or functional states. This complements the more commonly used activation approach to functional neuroimaging data, which characterize functionally specialized regions, and provides important data characterizing the functional interactions between these regions.

Aged↗

Optical coherence tomography: technology and applications for neuroimaging.

Optical coherence tomography (OCT) is an emerging imaging technology with applications in biology, medicine, and materials investigations. Attractive features include high cellular-level resolution, real-time acquisition rates, and spectroscopic feature extraction in a compact noninvasive instrument. OCT can perform "optical biopsies" of tissue, producing images approaching the resolution of histology without having to resect and histologically process tissue specimens for characterization and diagnosis. This article will review several of the current technological developments in OCT. To illustrate the potential of this technology for neuroimaging, applications for imaging neural development, the neural retina, tumors of the central nervous system, and the microsurgical repair of peripheral nerves will be presented. This technology offers a potential investigative tool for addressing many of the present challenges in neuroimaging.

Algorithms↗

Neuroimaging and presurgical evaluation of symptomatic epilepsies.

The goal of presurgical evaluation of intractable epilepsy is to identify epileptogenic regions in the brain. From our experience of 38 cases of resective epilepsy surgery from the last 3 years, ictal SPECT was considered the most sensitive at detecting focal changes relating to seizures compared to other neuroimaging modalities, such as MRI, FDG-PET, SPECT and MEG. At interictal state, on the other hand, FDG-PET was most sensitive, especially in cases with focal cortical dysplasia, which is often MRI-invisible. In dysplastic tumors, MRI showed the highest concordance rate to clinically verified epileptogenic regions. Activation studies using functional neuroimaging such as PET and fMRI is useful to evaluate brain functions at epileptogenic regions presurgically. The role of functional brain imaging in epilepsy surgery is considered to be: (i). case selection for resective surgery, (ii). case selection for invasive EEG monitoring, and (iii). navigation of electrode placement and cortical resection.

Brain↗

Association of minimal thickness of the medial temporal lobe with hippocampal volume, maximal and minimal hippocampal length: volumetric approach with horizontal magnetic resonance imaging scans for evaluation of a diagnostic marker for neuroimaging of Alzheimer's disease.

A 3-D volumetric study of the medial temporal lobe (MTL) was performed to evaluate how a minimum thickness of the MTL (mtMTL), a visually estimated measure, is associated with other MTL measures, maximal and minimal hippocampal length (max-HL, min-HL) and hippocampal volume, all measured with a 3-D device, Neurolucida, in 33 patients with Alzheimer's disease (AD), seven patients with mild cognitive impairment (MCI), and 20 age-matched controls. Cognitive impairment was evaluated with Mini-Mental State examination (MMSE). The T1-weighted horizontal magnetic resonance imaging (MRI) scans with slices 5 mm thick were analyzed with Neurolucida and the mtMTL was measured with visual estimation. The MTL was divided into the amygdala and hippocampus. Max-HL on both sides was longer in controls than in AD and MCI, whereas min-HL and mtMTL were longer in controls than in AD, and no difference was observed between MCI and controls. Similarly hippocampal volume was larger in controls than in AD, and no differences were seen within the MCI and controls. No difference in amygdala and midbrain volumes was observed among AD, MCI and controls. Correlation of MMSE score with min-HL and mtMTL was higher than that with max-HL. Although hippocampal and MTL measures examined here failed to show significant difference between AD and MCI, max-HL could be a diagnostic neuroimaging sign of AD. The high correlation of MMSE with mtMTL as well as with min-HL compared with that with max-HL, also will support neuroimaging diagnosis of AD.

Aged↗

The functional organization of working memory processes within human lateral frontal cortex: the contribution of functional neuroimaging.

Recent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cortex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal-lobe function, developed through lesion and electrophysiological recording work in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta-analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non-spatial working memory.

Animals↗

Surgery for intractable infantile spasms: neuroimaging perspectives.

Twenty-three infants and children underwent cortical resection (n = 15) or hemispherectomy (n = 8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow-up (range 4-67 months; mean 28.3 months), 15 children were seizure-free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.

Brain↗

Neuroimaging of bipolar disorder: emphasis on novel MRI techniques.

The explosion of neuroimaging in the last decade has contributed to a revision of the concept of bipolar disorder, which was traditionally seen as a cyclic illness with return to normality between episodes lacking "by default" permanent brain abnormalities. A conspicuous corpus of neuroimaging and neuropathology studies indicates that brain changes occur in bipolar disorder, although their etiology and their relation to clinical features are yet to be established. This review summarizes the results from magnetic resonance imaging studies using conventional and novel techniques in patients with bipolar disorder.

Bipolar Disorder↗

Neuroimaging findings in neurosyphilis.

We report two cases of neurosyphilis with atypical clinical presentations that were compounded by atypical neuroimaging findings. In the first case, MRI brain scan findings were felt to be compatible with mesial temporal sclerosis or herpes simplex encephalitis. The second patient presented with a clinical picture compatible with normal pressure hydrocephalus as well as some degree of ventricular enlargement and prominent periventricular white matter changes by MRI brain scan. He actually underwent ventriculo-peritoneal shunting prior to determination that he had active syphilitic involvement of the central nervous system. Neurosyphilis, "the great imitator," is not only capable of mimicking various other neurological disease clinical presentations, it can also mimic neuroimaging features of various other disease processes as well.

Adult↗

Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging.

New treatments for Alzheimer's disease (AD) are more likely to slow or halt disease progression rather than to reverse existing neuronal damage. Identifying persons with mild cognitive complaints who are at risk for AD will allow investigators to apply anti-dementia treatments before extensive brain damage develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4) as a major risk factor for AD offers promise of assisting in early detection and prediction of Alzheimer's disease, particularly when genetic assessments are combined with other biomarkers such as neuroimaging. Studies of relatives at risk for familial AD using neuroimaging (positron emission tomography [PET]) and genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4 have lower parietal metabolism than those without APOE epsilon 4. Additional techniques that might increase sensitivity and specificity include longitudinal assessment of clinical and brain functional change, pharmacological challenges of short-acting anticholinergic agents, and memory activation paradigms during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental anti-dementia treatment trials.

Adult↗

Neuroimaging characteristics in carbon monoxide toxicity.

Neuroimaging studies for 18 patients carrying carbon monoxide toxicity as a discharge diagnosis were reviewed. The most common positive findings were low-density lesions in the globus pallidus (7/18, 39%) and deep white matter changes (5/18, 28%). Six computed tomography head scans showed no acute changes. Advanced age, method of exposure (intentional vs accidental), and severity of carboxyhemoglobin level did not predict neuroradiological or clinical outcomes. Early neuroimaging could not be used to predict clinical courses (death or coma vs discharge to either an institution or a home) in the patient population studied.

Accidents↗

Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation.

This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.

Adenocarcinoma↗

Neuroimaging in child and adolescent psychiatric disorders.

Neuroimaging in child psychiatry is a rapidly developing field and the number of different techniques being used is increasing rapidly. This review describes the current status of neuroimaging in childhood psychopathology and discusses limitations of the various studies. As yet, no specific and consistent abnormality has been detected in childhood psychiatric disorders. Obsessive compulsive disorder has shown the most consistent findings so far, with orbitofrontal cortex and the caudate nucleus being implicated. Better understanding of the corticostriatal neural networks will shed more light on the neurodevelopmental disorders of childhood.

Adolescent↗

BrainImageJ: a Java-based framework for interoperability in neuroscience, with specific application to neuroimaging.

The Human Brain Project consortium continues to struggle with effective sharing of tools. To facilitate reuse of its tools, the Stanford Psychiatry Neuroimaging Laboratory (SPNL) has developed BrainImageJ, a new software framework in Java. The framework consists of two components-a set of four programming interfaces and an application front end. The four interfaces define extension pathways for new data models, file loaders and savers, algorithms, and visualization tools. Any Java class that implements one of these interfaces qualifies as a BrainImageJ plug-in-a self-contained tool. After automatically detecting and incorporating new plug-ins, the application front end transparently generates graphical user interfaces that provide access to plug-in functionality. New plug-ins interoperate with existing ones immediately through the front end. BrainImageJ is used at the Stanford Psychiatry Neuroimaging Laboratory to develop image-analysis algorithms and three-dimensional visualization tools. It is the goal of our development group that, once the framework is placed in the public domain, it will serve as an interlaboratory platform for designing, distributing, and using interoperable tools.

Algorithms↗

Review of a mock research protocol in functional neuroimaging by Canadian research ethics boards.

OBJECTIVE: To examine how research ethics boards (REBs) review research projects in emerging disciplines such as functional neuroimaging. DESIGN: To compare the criteria applied and the decisions reached by REBs that reviewed the same mock research protocol in functional neuroimaging. PARTICIPANTS: 44 Canadian biomedical REBs, mostly working in public university or hospital settings. MAIN MEASUREMENTS: The mock research protocol "The Neurobiology of Social Behavior" included several ethical issues operating at all three levels: personal, institutional and social. Data consisting of responses to closed questions were analysed quantitatively. Qualitative analysis of open-question responses used mixed classification. RESULTS: Similar criteria were used by most participating REBs. Yet the project was unconditionally approved by 3 REBs, approved conditionally by 10 and rejected by 30. CONCLUSIONS: The results point to the difficulty for REBs of reviewing all kinds of research projects, regardless of field, by relying on international and national norms framed in general terms and a possible variation between REBs in the interpretation of their mandate for the protection of research subjects.

Canada↗

Are investigations anxiolytic or anxiogenic? A randomised controlled trial of neuroimaging to provide reassurance in chronic daily headache.

OBJECTIVES: Aims were to investigate (a) whether neuroimaging in patients with chronic daily headache reassures patients or fails to reassure them and/or worsens outcome, impacting on service use, costs, health anxieties, and symptoms, and (b) whether this reassurance process occurs differentially in patients with different levels of psychological morbidity. METHODS DESIGN: randomised controlled trial; setting: headache clinic in secondary care, South London; participants: 150 patients fulfilling criteria for chronic daily headache, stratified using the Hospital Anxiety and Depression Scale (HADS); intervention: treatment as usual or the offer of an MRI brain scan; main outcome measures: use of services, costs, and health anxiety. RESULTS: Seventy six patients were randomised to the offer of a brain scan and 74 patients to treatment as usual. One hundred and thirty seven (91%) primary care case notes were examined at 1 year, 103 (69%) patients completed questionnaires at 3 months and 96 (64%) at 1 year. Sixty six (44%) patients were HADS positive (scored >11 on either subscale). Patients offered a scan were less worried about a serious cause of the headaches at 3 months (p = 0.004), but this was not maintained at 1 year; other health anxiety measures did not differ by scan status. However, at 1 year HADS positive patients offered a scan cost significantly less, by 465 pounds Sterling (95% confidence interval (CI): -1028 pounds Sterling to -104 pounds Sterling), than such patients not offered a scan, due to lower utilisation of medical resources. CONCLUSIONS: Neuroimaging significantly reduces costs for patients with high levels of psychiatric morbidity, possibly by changing subsequent referral patterns of the general practitioner.

Adult↗

CSF biomarkers in frontotemporal lobar degeneration: relations with clinical characteristics, apolipoprotein E genotype, and neuroimaging.

In order to better understand the large variation in cerebrospinal fluid (CSF) tau and amyloid-beta(1-42) (Abeta42) in frontotemporal lobar degeneration (FTLD), relations between these biomarkers and clinical parameters, neuroimaging characteristics, and apolipoprotein E (ApoE) genotype were studied in 31 patients with FTLD, including 16 patients with the frontal variant and 15 with the temporal variant. CSF tau was highest in FTLD with predominant temporal involvement. In the frontal subgroup, CSF tau level was influenced by the number of ApoE epsilon3 alleles. In the temporal subgroup, CSF tau level was dependent on a combination of CSF Abeta42, age, disease duration, and disease severity. No relation with degree of atrophy or asymmetry on neuroimaging could be established. CSF Abeta42 variability remained unexplained. Future research could study the role of ApoE genotype and Abeta42 in FTLD, as well as establish measures for disease intensity.

Age Factors↗