Cortical Deactivations Research Articles

Changes in working memory-related cortical responses following pediatric mild traumatic brain injury: A longitudinal fMRI study

Persistent post-concussion symptoms (PPCS) lasting longer than 4 weeks affect 25% of children with mild traumatic brain injury (mTBI) or concussion. Working memory (WM) problems are a common complaint in children with PPCS. Despite normal function on traditional neuropsychological tests, these children exhibit aberrant cortical responses within the dorsolateral prefrontal cortex (dlPFC) and default mode network (DMN) regions – both of which are implicated in WM. Using a prospective, longitudinal cohort study design, we investigated changes in cortical fMRI responses within the dlPFC and DMN during an nback WM task at two timepoints: one and two months post-injury. Across these timepoints, the primary outcome was change in cortical activations (increase in BOLD) and deactivations (decrease in BOLD) of both dlPFC and DMN. Twenty-nine children (mean age 15.49 ± 2.15; 48.3% male) with fMRI scans at both timepoints were included, following data quality control. Student’s t-tests were used to examine cortical activations across time and task difficulty. ANCOVA F-tests examined cortical responses after removal of baseline across time, task difficulty and recovery. Volumes of interest (5 mm sphere) were placed in peak voxel regions of the DMN and dlPFC to compare cortical responses between recovered and unrecovered participants over time (one-way ANOVA). Between one and two months post-injury, we found significant increases in dlPFC activations and significant activations and deactivations in the DMN with increasing task difficulty, alongside improved task performance. Cortical responses of the DMN and bilateral dlPFC displayed increased intensity in recovered participants, together with improved attention and behavioural symptoms. Overall, our findings suggest evidence of neural compensation and ongoing cognitive recovery from pediatric TBI over time between one and two months post injury in children with PPCS. These results highlight the wider and persisting implications of mTBI in children, whose maturing brains are particularly vulnerable to TBI.

Functional MRI of arousals in nonrapid eye movement sleep.

Arousals commonly occur during human sleep and have been associated with several sleep disorders. Arousals are characterized as an abrupt electroencephalography (EEG) frequency change to higher frequencies during sleep. However, the human brain regions involved in arousal are not yet clear. Simultaneous EEG and functional magnetic resonance imaging (fMRI) data were recorded during the early portion of the sleep period in healthy young adults. Arousals were identified based on the EEG data, and fMRI signal changes associated with 83 arousals from 19 subjects were analyzed. Subcortical regions, including the midbrain, thalamus, basal ganglia, and cerebellum, were activated with arousal. Cortices, including the temporal gyrus, occipital gyrus, and frontal gyrus, were deactivated with arousal. The activations associated with arousal in the subcortical regions were consistent with previous findings of subcortical involvement in behavioral arousal and consciousness. Cortical deactivations may serve as a mechanism to direct incoming sensory stimuli to specific brain regions, thereby monitoring environmental perturbations during sleep.

Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls.

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

Networks underlying paroxysmal fast activity and slow spike and wave in Lennox-Gastaut syndrome

To use EEG-fMRI to determine which structures are critically involved in the generation of paroxysmal fast activity (PFA) and slow spike and wave (SSW) (1.5-2.5 Hz), the characteristic interictal discharges of Lennox-Gastaut syndrome (LGS). We studied 13 well-characterized patients with LGS using structural imaging and EEG-fMRI at 3 tesla. Ten patients had cortical structural abnormalities. PFA and SSW were considered as separate events in the fMRI analysis. Simultaneous with fMRI, PFA was recorded in 6 patients and SSW in 9 (in 2, both were recorded). PFA events showed almost uniform increases in blood oxygen level-dependent (BOLD) signal in "association" cortical areas, as well as brainstem, basal ganglia, and thalamus. SSW showed a different pattern of BOLD signal change with many areas of decreased BOLD signal, mostly in primary cortical areas. Two patients with prior callosotomy had lateralized as well as generalized PFA. The lateralized PFA was associated with a hemispheric version of the PFA pattern we report here. PFA is associated with activity in a diffuse network that includes association cortices as well as an unusual pattern of simultaneous activation of subcortical structures (brainstem, thalamus, and basal ganglia). By comparison, the SSW pattern is quite different, with cortical and subcortical activations and deactivations. Regardless of etiology, it appears that 2 key, but distinct, patterns of diffuse brain network involvement contribute to the defining electrophysiologic features of LGS.

Combined structural and functional imaging reveals cortical deactivations in grapheme-color synaesthesia

Synaesthesia is a heritable condition in which particular stimuli generate specific and consistent sensory percepts or associations in another modality or processing stream. Functional neuroimaging studies have identified potential correlates of these experiences, including, in some but not all cases, the hyperactivation of visuotemporal areas and of parietal areas thought to be involved in perceptual binding. Structural studies have identified a similarly variable spectrum of differences between synaesthetes and controls. However, it remains unclear the extent to which these neural correlates reflect the synaesthetic experience itself or additional phenotypes associated with the condition. Here, we acquired both structural and functional neuroimaging data comparing thirteen grapheme-color synaesthetes with eleven non-synaesthetes. Using voxel-based morphometry and diffusion tensor imaging, we identify a number of clusters of increased volume of gray matter, of white matter or of increased fractional anisotropy in synaesthetes vs. controls. To assess the possible involvement of these areas in the synaesthetic experience, we used nine areas of increased gray matter volume as regions of interest in an fMRI experiment that characterized the contrast in response to stimuli which induced synaesthesia (i.e., letters) vs. those which did not (non-meaningful symbols). Four of these areas showed sensitivity to this contrast in synaesthetes but not controls. Unexpectedly, in two of them, in left lateral occipital cortex and in postcentral gyrus, the letter stimuli produced a strong negative BOLD signal in synaesthetes. An additional whole-brain fMRI analysis identified 14 areas, three of which were driven mainly by a negative BOLD response to letters in synaesthetes. Our findings suggest that cortical deactivations may be involved in the conscious experience of internally generated synaesthetic percepts.

FC25-02 - Functional MRI activation in response to panic-specific, non-panic aversive, and neutral imagery in patients with panic disorder and healthy controls

IntroductionThere is evidence that, besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder.Objectives and aimsUsing fMRI, this study investigated BOLD response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy controls. Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex.Methods21 PDA subjects (12 female, 9 male) and 21 matched controls were investigated using a Siemens 3 T scanner. Before, PDA subjects gave ratings on 120 pictures showing characteristic panic/agoraphobia situations (PA). 20 pictures with the individually highest ratings were selected. 20 matching pictures showing aversive but not panic-specific stimuli (A) and 80 neutral pictures (N) from the International Affective Picture-System (IAPS) were chosen for each subject. Anxiety and depression ratings were recorded.ResultsGroup comparisons revealed a significantly greater BOLD response in PDA subjects than in controls in the insular cortices, left inferior frontal gyrus, dmPFC, the left hippocampal formation, and left caudatum (p < .005), when PA and N responses were compared. Group comparisons for stimulation with A compared to PA showed activation of similar brain regions in both groups but with different peak coordinates.ConclusionsResults indicate specific activation patterns to panic-specific picture stimulation in PDA patients. Distinct peak coordinates between PA and A differ between groups. This might implicate that the brain circuits underlying processing of aversive stimuli might differ in their function in PDA patients compared to healthy subjects.

Absence seizures: Individual patterns revealed by EEG‐fMRI

Absences are characterized by an abrupt onset and end of generalized 3-4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences. Seventeen absences from nine patients with absence epilepsy and classical pattern of 3-4 Hz GSWs during EEG-fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen-level dependent (BOLD) response maps. Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient-specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses. Like a fingerprint, patient-specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific.

Abnormal Regional Brain Activity During Rest and (Anticipated) Gastric Distension in Functional Dyspepsia and the Role of Anxiety: A H2 15O-PET Study

During gastric distension in hypersensitive functional dyspepsia (FD), activation was found in somatosensory cortex (SI/SII) and ventrolateral prefrontal cortex (vlPFC) but, contrary to controls, not in pregenual anterior cingulate (pACC). The aims of this article were to study (i) cortical activations and deactivations during distension and sham compared with baseline in FD, regardless of sensitivity status; (ii) differences in brain activity between health and FD during "no distension" conditions; and (iii) the relationship between anxiety and brain activity in FD. Brain H(2)(15)O-PET was performed in 25 FD patients (13 hypersensitive) during three conditions: baseline, distension at discomfort threshold, and sham. Brain activity was compared against healthy controls using SPM2. Discomfort threshold was lower; sensation scores in all conditions were higher in patients than controls. (i) Activations were similar to controls, except for a lack of pACC activation during distension in FD. Patients showed no dorsal pons and amygdala deactivation during distension and sham, respectively. (ii) Comparing baseline or sham activity showed the following differences: higher activity in SII/SI, insula, midcingulate (MCC), dorsolateral and ventrolateral PFC in controls; and higher activity in occipital cortex in FD. Differences in left lateral PFC were specific to sham. (iii) Anxiety correlated negatively with pACC and MCC and positively with dorsal pons activity. FD patients failed to activate pACC, to deactivate dorsal pons during distension, and to deactivate amygdala during sham; this may represent arousal-anxiety-driven failure of pain modulation. During baseline and sham, differences between patients and controls were found in sensory as well as affective-cognitive areas.

Dysfunction of the Default Mode Network in Parkinson Disease

To examine the integrity of the default mode network in patients with Parkinson disease (PD). Previous functional neuroimaging experiments have studied executive deficits in patients with PD with regard to task-related brain activation. However, recent studies suggest that executive performance also relies on the integrity of the default mode network (ie, medial prefrontal cortex, posterior cingulate cortex, precuneus, and lateral parietal and medial temporal cortices), characterized by a deactivation of these cortical areas during the performance of executive tasks. We used functional magnetic resonance imaging to investigate cortical deactivations during a card-sorting task (retrieval and manipulation of short-term memory contents) compared with a simple sensory-motor matching task. In addition, a functional connectivity analysis was performed. Tertiary outpatient clinic. Seven patients with mild to moderate PD (not taking medication) and 7 healthy controls. Cortical deactivations. Both groups showed comparable deactivation of the medial prefrontal cortex but different deactivation in the posterior cingulate cortex and the precuneus. Compared with controls, patients with PD not only showed less deactivation of the posterior cingulate cortex and the precuneus, they even demonstrated a reversed pattern of activation and deactivation. Connectivity analysis yielded that in contrast to healthy individuals, medial prefrontal cortex and the rostral ventromedial caudate nucleus were functionally disconnected in PD. We describe specific malfunctioning of the default mode network during an executive task in PD. This finding is plausibly linked to dopamine depletion and may critically contribute to the understanding of executive deficits in PD.

Cortical deactivations during gastric fundus distension in health: visceral pain‐specific response or attenuation of ‘default mode’ brain function? A H215O‐PET study

Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H(2) (15)O-brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C(1)) no distension (baseline); isobaric distension to individual thresholds for (C(2)) first, (C(3)) marked, (C(4)) unpleasant sensation and (C(5)) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P(uncorrected_voxel_level) < 0.001 and P(corrected_cluster_level) < 0.05. Baseline-maximal distension (C(1)-C(4)) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso- and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task-independent suspension of 'default mode' activity (as described in various cognitive tasks) or an visceral pain/interoception-specific process remains to be elucidated.

T1466 The Neurophysiology of Gastric Sensation in Health: A Role for Cortical Deactivations?

T1466 The Neurophysiology of Gastric Sensation in Health: A Role for Cortical Deactivations?

Functional impact of primary visual cortex deactivation on subcortical target structures in the thalamus and midbrain

The functional relationships between the primary visual cortex and its major subcortical target structures have long been a subject of interest. We studied these relationships by using localized cooling deactivation to silence portions of primary visual cortex and measuring 2-deoxyglucose (2DG) uptake to assess neural activity in subcortical and midbrain targets. We focused analysis on the largest subcortical targets of primary visual cortex: the superior colliculus (SC), the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the lateral division of the lateral posterior nucleus of the thalamus (LPL). We found that localized cooling of different regions of primary visual cortex caused specific decreases in 2DG uptake in target structures such that the location of 2DG decrease varied according to joint retinotopy, and the magnitude of the decreases in target structures was associated with the amount of cooled cortex. In addition, we found that the impact of cortical cooling was more profound on the SC than on the dLGN. The functional impact of cortical deactivations on the LPL was weak for small deactivations but approximated the impact on the SC when deactivations were large. We discuss these findings in terms of neural circuits and in terms of drivers and modulators.

Differential limbic–cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders

Background: Affective disorders are associated with comorbidity of depression and anxiety symptoms. Positron emission tomography resting-state studies in affective disorders have generally failed to isolate specific symptom effects. Emotion provocation studies in healthy volunteers have produced variable results, due to differences in experimental paradigm and instructions. Methods: To better delineate the neural correlates of sad mood and anxiety, this study used autobiographical memory scripts in eight healthy women to generate sadness, anxiety, or a neutral relaxed state in a within-subject design. Results: Sadness and anxiety, when contrasted to a neutral emotional state, engaged a set of distinct paralimbic–cortical regions, with a limited number of common effects. Sadness was accompanied by specific activations of the subgenual cingulate area (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7. Anxiety was associated with specific activations of the ventral insula, the orbitofrontal and anterior temporal cortices, specific deactivation of parahippocampal gyri, and more prominent deactivation of the inferior temporal cortex BAs 20/37. Conclusions: These findings are interpreted within a model in which sadness and anxiety are represented by segregated corticolimbic pathways, where a major role is played by selective dorsal cortical deactivations during sadness, and ventral cortical deactivations in anxiety.