Nick F. Ramsey

Statistical analysis of functional MRI data in the wavelet domain

The use of the wavelet transform is explored for the detection of differences between brain functional magnetic resonance images (fMRIs) acquired under two different experimental conditions. The method benefits from the fact that a smooth and spatially localized signal can be represented by a small set of localized wavelet coefficients, while the power of white noise is uniformly spread throughout the wavelet space. Hence, a statistical procedure is developed that uses the imposed decomposition orthogonality to locate wavelet-space partitions with large signal-to-noise ratio (SNR), and subsequently restricts the testing for significant wavelet coefficients to these partitions. This results in a higher SNR and a smaller number of statistical tests, yielding a lower detection threshold compared to spatial-domain testing and, thus, a higher detection sensitivity without increasing type I errors. The multiresolution approach of the wavelet method is particularly suited to applications where the signal bandwidth and/or the characteristics of an imaging modality cannot be well specified. The proposed method was applied to compare two different fMRI acquisition modalities, Differences of the respective useful signal bandwidths could be clearly demonstrated; the estimated signal, due to the smoothness of the wavelet representation, yielded more compact regions of neuroactivity than standard spatial-domain testing.

Effects of frequent cannabis use on hippocampal activity during an associative memory task

Interest is growing in the neurotoxic potential of cannabis on human brain function. We studied non-acute effects of frequent cannabis use on hippocampus-dependent associative memory, investigated with functional Magnetic Resonance Imaging (fMRI) in 20 frequent cannabis users and 20 non-users matched for age, gender and IQ. Structural changes in the (para)hippocampal region were measured using voxel-based morphometry (VBM). Cannabis users displayed lower activation than non-users in brain regions involved in associative learning, particularly in the (para)hippocampal regions and the right dorsolateral prefrontal cortex, despite normal performance. VBM-analysis of the (para)hippocampal regions revealed no differences in brain tissue composition between cannabis users and non-users. No relation was found between (para)hippocampal tissue composition and the magnitude of brain activity in the (para)hippocampal area. Therefore, lower brain activation may not signify neurocognitive impairment, but could be the expression of a non-cognitive variable related to frequent cannabis use, for example changes in cerebral perfusion or differences in vigilance.

Functional Mapping of Human Sensorimotor Cortex with 3D BOLD fMRI Correlates Highly With H215O PET rCBF

Positron emission tomography (PET) functional imaging is based on changes in regional cerebral blood flow (rCBF). Functional magnetic resonance imaging (fMRI) is based on a variety of physiological parameters as well as rCBF. This study is aimed at the cross validation of three-dimensional (3D) fMRI, which is sensitive to changes in blood oxygenation, with oxygen-15-labeled water (H215O) PET. Nine normal subjects repeatedly performed a simple finger opposition task during fMRI scans and during PET scans. Within-subject statistical analysis revealed significant (“activated”) signal changes (p < 0.05, Bonferroni corrected for number of voxels) in contralateral primary sensorimotor cortex (PSM) in all subjects with fMRI and with PET. With both methods, 78% of all activated voxels were located in the PSM. Overlap of activated regions occurred in all subjects (mean 43%, SD 26%). The size of the activated regions in PSM with both methods was highly correlated (rho = 0.87, p < 0.01). The mean distance between centers of mass of the activated regions in the PSM for fMRI versus PET was 6.7 mm (SD 3.0 mm). Average magnitude of signal change in activated voxels in this region, expressed as z-values adapted to timeseries, zt, was similar (fMRI 5.5, PET 5.3). Results indicate that positive blood oxygen level-dependent (BOLD) signal changes obtained with 3D principles of echo shifting with a train of observations (PRESTO) fMRI are correlated with rCBF, and that sensitivity of fMRI can equal that of H215O PET.

Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research.

Over the last decade there has been a steady increase in the prevalence of frequent cannabis use among teenagers, accompanied by a decrease in age of first use. Evidence from both animal and human studies suggests that the severity of the effects of cannabis use on cognitive development is dependent on the age when cannabis use begins. One possible explanation is that those who begin cannabis use early in adolescence are more likely to become heavily dependent. It is plausible that chronic cannabis abuse will then interfere with educational and vocational training. From a more biological perspective, however, use of cannabis during critical developmental periods in the still maturing brain may induce persistent alterations in brain structure and brain function. Therefore, the effects of frequent cannabis use during adolescence could be different from and more serious than during adulthood, an issue increasingly recognized in the field of cannabis research. In this paper we review the relevant animal and human literature on long-term effects of frequent exposure to cannabis during adolescence on the development of cognition, brain structure and function, and discuss implications, methodological and conceptual issues, and future prospects.

The role of functional magnetic resonance imaging in brain surgery.

New functional neuroimaging techniques are changing our understanding of the human brain, and there is now convincing evidence to move away from the classic and clinical static concepts of functional topography. In a modern neurocognitive view, functions are thought to be represented in dynamic large-scale networks. The authors review the current (limited) role of functional MR imaging in brain surgery and the possibilities of new functional MR imaging techniques for research and neurosurgical practice. A critique of current clinical gold standard techniques (electrocortical stimulation and the Wada test) is given.

Activation of striate cortex in the absence of visual stimulation: An fMRI study of synesthesia.

It has been suggested that internally generated visual perception involves the primary visual cortex V1. To test this hypothesis, a functional MRI study was conducted with a female subject with orthographic color–word synesthesia. This subject was selected as she reported clear involuntary visualization of auditorily presented verbal material. Hearing a word resulted in seeing the word in a particular color. fMRI scans were acquired while the subject performed two verbal tasks (passive listening to words and verbal fluency). Significant activity was detected in primary visual cortex, in the absence of external visual stimulation. This finding provides evidence for a role of modulatory feedback connections between associative and primary visual areas in visual experience without direct visual stimulation.

Reproducibility of human 3D fMRI brain maps acquired during a motor task

This study is an investigation into the reproducibility of brain activation in the sensorimotor cortex obtained with 3D “PRESTO” fMRI on eleven normal subjects. During one session, two series of functional scans were acquired while the subjects performed a finger opposition task (2 Hz). Nine subjects were tested once more on a different day. Each individual motor trial was analyzed separately, with a conservative zt‐based method. Using these results, the agreement between repeated series was examined in a number of ways, comparing the two series within one session, and the two series across sessions. In 28 of the 31 series (90%) significant signal change was found in the contralateral primary sensorimotor cortex (PSM). Overall, 0.20% of all voxels (total about 11,000) in the scanned volume reached significance, and approximately 60% of the significant positive signal changes were located in the PSM (P < 5 x 10‐7 for a chance occurrence). Comparisons within and across sessions yielded similar results: there was a 20–30% overlap of the clusters of activated voxels in the PSM (chance overlap within the PSM: P < 0.01). The mean distance between zt‐weighted centers of mass was 4.0–4.4 mm (chance distance within the PSM: P = 0.033 and 0.058, respectively). No significant difference was found between series in the magnitude of significant signal change. Whereas the number of activated voxels in the PSM was not consistently correlated between series, the ratio of this number over the total number of activated voxels in the scanned volume was significantly correlated (rho = 0.75–0.79, P < 0.05). These results indicate that activation in sensorimotor cortex associated with oppositional finger movement is reliably mapped with 3D PRESTO fMRI. (This article is a US Government work and, as such, is in the public domain in the United States of America.)

Fully Implanted Brain–Computer Interface in a Locked-In Patient with ALS

Options for people with severe paralysis who have lost the ability to communicate orally are limited. We describe a method for communication in a patient with late-stage amyotrophic lateral sclerosis (ALS), involving a fully implanted brain-computer interface that consists of subdural electrodes placed over the motor cortex and a transmitter placed subcutaneously in the left side of the thorax. By attempting to move the hand on the side opposite the implanted electrodes, the patient accurately and independently controlled a computer typing program 28 weeks after electrode placement, at the equivalent of two letters per minute. The brain-computer interface offered autonomous communication that supplemented and at times supplanted the patients eye-tracking device. (Funded by the Government of the Netherlands and the European Union; ClinicalTrials.gov number, NCT02224469 .).

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine.

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.

BOLD specificity and dynamics evaluated in humans at 7 T: comparing gradient-echo and spin-echo hemodynamic responses.

High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (∼1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III–IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.