Richard D. Hichwa

Subcortical and cortical brain activity during the feeling of self-generated emotions

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organisms continuously changing internal state.

Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naïve patients

BACKGROUND There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). METHODS We studied 17 neuroleptic-naïve patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. FINDINGS An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. INTERPRETATION These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.

A role for left temporal pole in the retrieval of words for unique entities

Both lesion and functional imaging studies have implicated sectors of high‐order association cortices of the left temporal lobe in the retrieval of words for objects belonging to varied conceptual categories. In particular, the cortices located in the left temporal pole have been associated with naming unique persons from faces. Because this neuroanatomical‐behavioral association might be related to either the specificity of the task (retrieving a name at unique level) or to the possible preferential processing of faces by anterior temporal cortices, we performed a PET imaging experiment to test the hypothesis that the effect is related to the specificity of the word retrieval task. Normal subjects were asked to name at unique level entities from two conceptual categories: famous landmarks and famous faces. In support of the hypothesis, naming entities in both categories was associated with increases in activity in the left temporal pole. No main effect of category (faces vs. landmarks/buildings) or interaction of task and category was found in the left temporal pole. Retrieving names for unique persons and for names for unique landmarks activate the same brain region. These findings are consistent with the notion that activity in the left temporal pole is linked to the level of specificity of word retrieval rather than the conceptual class to which the stimulus belongs. Hum. Brain Mapping 13:199–212, 2001.

Neural Correlates of Naming Actions and of Naming Spatial Relations

Ina [(15)O] water PET experiment, 10 normal subjects retrieved words denoting actions (performed with or without an implement), and another 10 normal subjects retrieved words denoting the spatial relations between objects. Our objective was to test the following hypothesis: that the salient neural activity associated with naming actions and spatial relations occurs in left frontal operculum and left parietal association cortices, but not in the left inferotemporal cortices (IT) or in the right parietal association cortices. There were two control tasks, one requiring a decision on the orientation of unknown faces (a standard control task in our laboratory) and another requiring the retrieval of words denoting the concrete entities used in the action and spatial relations tasks. In accordance with the hypothesis, both naming actions and spatial relations (using the face orientation task as control activated the left frontal operculum; naming actions also activated the left parietal lobe. However, sectors of the left posterior IT were also engaged in both naming actions and spatial relations. When the naming of concrete entities was subtracted from the naming of actions performed with such entities, area MT in the posterior temporo-occipital region was activated bilaterally. On the other hand, when naming of the concrete entities was subtracted from the naming of spatial relations, left parietal activation was found, and when two tasks of naming spatial relations were contrasted to each other bilateral parietal activation was seen, right when abstract stimuli were used and left when concrete objects were used. The activity in posterior IT is thought to be related to object processing and possibly name retrieval at a subconscious level.

The Cerebellum and Emotional Experience

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

Effects of Smoking Marijuana on Brain Perfusion and Cognition

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [15Oxygen]-labeled water ([15O]H2O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in “paralimbic” regions and may be related to marijuanas mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Effects of frequent marijuana use on memory-related regional cerebral blood flow.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding. In learning a word list to criterion over multiple trials, marijuana users, relative to control subjects, required means of 2.7 more presentations during initial learning and 3.1 more presentations during subsequent relearning. In single-trial recall, marijuana users appeared to rely more on short-term memory, recalling 23% more than control subjects from the end of a list, but 19% less from the middle. These findings indicate altered memory-related brain function in marijuana users.

A Positron Emission Tomography Study of Binaurally and Dichotically Presented Stimuli: Effects of Level of Language and Directed Attention

Regional cerebral blood flow (rCBF) was measured using positron emission tomography with oxygen- 15 labeled water as 10 normal subjects listened to three types of auditory stimuli (environmental sounds, meaningless speech, and words) presented binaurally or dichotically. Binaurally presented environmental sounds and words caused similar bilateral rCBF increases in left and right superior temporal gyri. Dichotically presented stimuli (subjects attended to left or right ears) caused asymmetric activation in the temporal lobes, resulting from increased rCBF in temporal lobe regions contralateral to the attended ear and decreased rCBF in the opposite hemisphere. The results indicate that auditorily presented language and non-language stimuli activate similar temporal regions, that dichotic stimulation dramatically changes rCBF in temporal lobes, and that the change is due both to attentional mechanisms and to hemispheric specialization.

The cerebellum plays a role in conscious episodic memory retrieval.

The cerebellum has traditionally been considered to be primarily dedicated to motor functions. Its phylogenetic development and connectivity suggest, however, that it also may play a role in cognitive processes in the human brain. In order to examine a potential cognitive role for the cerebellum in human beings, a positron emission tomography (PET) study was conducted during a “pure thought experiment”: subjects intentionally recalled a specific past personal experience (consciously retrieved episodic memory). Since there was no motor or sensory input or output, the design eliminated the possibility that cerebellar changes in blood flow were due to motor activity. During silent recall of a consciously retrieved episodic memory, activations were observed in the right lateral cerebellum, left medial dorsal thalamus, medial and left orbital frontal cortex, anterior cingulate, and a left parietal region. These activations confirm a cognitive role for the cerebellum, which may participate in an interactive cortical‐cerebellar network that initiates and monitors the conscious retrieval of episodic memory. Hum. Brain Mapping 8:226–234, 1999.

II. PET Studies of Memory: Novel versus Practiced Free Recall of Word Lists

Positron emission tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60 s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or tasks-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.