Interval timing errors in a patient with thalamic chronotaraxis.

Thalamic chronotaraxis is an isolated disorientation of time caused by the damage of thalamus, especially the mediodorsal nucleus. We performed interval timing trials on a patient with this phenomenon. Based on the results of those trials and compared to the previous reports, thalamic chronotaraxis of our case might be due to the disfunction of the dorsolateral prefrontal cortex caused by the right thalamic infarction.

Dear Editor

Isolated time disorientation caused by a thalamic lesion is known as thalamic chronotaraxis [1], [2]. We report a case of thalamic chronotaraxis in which interval timing might have disclosed a subclinical time sense disturbance.

One morning, a 67-year-old right-handed woman experienced light-headedness. She received a phone call from her office, informing her that she was about 10 min late for work. When she arrived at the office, her colleague noticed mild dysarthria. Although she had never been late for work prior to this incident, she exhibited occasional misunderstandings of the daily schedules for several weeks thereafter. She visited our hospital one month after the onset of her symptoms.

Her past history was unremarkable except for hypertension. At the time of her first examination, she was alert and oriented, except for the month. Although she was able to continue her regular work, her son reported that she had become slightly forgetful. A 99mTc-ethylcysteinate dimer single-photon emission computed tomography (SPECT) revealed mild hypoperfusion in the right dorsolateral frontal cortex and the right thalamus (Fig. 1). Magnetic resonance imaging demonstrated a right thalamic lesion that included the intermediate and lateral part of the mediodorsal (MD) nucleus (Fig. 1) [2].

Fig. 1

T2-weighted MR images of the patient show a right medial thalamic infarct including the mediodorsal (MD) and ventral lateral (VL) nuclei (A). A SPECT scan shows hypoperfusion of the lateral frontal cortex and thalamus on the right side (B).

The patient's Revised Addenbrooke's Cognitive Examination score was 90/100 (attention and orientation, 17/18; memory, 20/26; fluency, 12/14; language, 26/26; and visuospatial, 15/16). She received a score of 6 for a forward digit span and a score of 3 for a backward digit span. Her scores for each index of the Wechsler Memory Scale-Revised (WMS-R) were as follows: verbal, 111; visual, 115; general, 113; attention/concentration, 104; and delayed recall, 112. Her Frontal Assessment Battery score was 13/18. On the Wisconsin Card Sorting Test, she achieved two categories without perseverative error.

After an explanation that the patient would be asked to estimate time durations (namely, a prospective paradigm), we performed several time-judgement trials. For the simple time production task, the patient was asked to indicate when she thought one of several randomly predetermined time intervals was over. She responded at 3.1 s when asked to respond after a predetermined time of 5 s, at 7.7 s for 15 s, at 15.8 s for 30 s, and at 27.6 s for 60 s. She stated that she had been counting off every second in her mind during the time production tasks.

In a time reproduction and verbal estimation task, she was asked to view a randomly presented figure on a computer screen without performing any action (low load condition). The figures were presented for several durations. After each presentation, she was instructed to indicate when she thought the same duration was over and to estimate the duration verbally. For a predetermined period of 5 s, she responded at 3.7 s and estimated the period to be 4 s. After that, she provided verbal estimates of the time intervals wrongly before reproductions. She judged a 15-s period as being 20 s and responded at 8.7 s, and she judged a 30-s period as being 42 s and responded at 23.8 s.

For verbal estimation trials performed under a high load condition [3], the patient was asked to estimate the duration of a trial during which she was required to read aloud number stimuli (1–9) on a computer screen. The stimuli were randomly presented throughout each predetermined interval. The rates of the stimulus presentations varied. Each time interval was presented twice in a random sequence of 10 trials. The patient judged 10 s as being 5 s and 7 s, 30 s as being 15 s and 10 s, 60 s as being 30 s and 40 s, 90 s as being 40 s and 50 s, and 120 s as being 50 s.

To interpret results for interval timing in the supra-second range, the pacemaker accumulator model has been proposed [4], [5], [6]. In this model, accumulated pulses emitted by a pacemaker (an internal clock) are counted and compared with a previously stored pulse record, enabling an appropriate response for time judgements to be achieved [5]. Based on this model, an accelerated internal clock might explain the interval timing results in the present case: i.e., rapid accumulation during the instructed duration might lead to under-production, and high accumulation during a confined interval might lead to over-estimation [6]. In addition, since the timing process necessitates attentional and mnemonic resources, when the accompanying cognitive load during prospective duration judgement becomes heavier (passive viewing versus active responding), the resources available for allocation to temporal information processing might decrease leading to verbal under-estimation, as in our case [5], [7].

Mimura et al. examined prospective verbal time estimations in patients with frontal lobe damage and alcoholic Korsakoff patients [3]. They speculated that the impaired episodic memory of Korsakoff patients might curtail longer time estimations. Although the results for the present patient were similar to those of Korsakoff patients in regard to an increase in under-estimation as the test intervals lengthened, she did not show any memory impairment on the WMS-R. Meanwhile, Koch et al. performed the same trials in a patient with an ischemic lesion in the right dorsolateral prefrontal cortex (DLPFC), who exhibited an impairment of time estimation for daily events [8]. Based on their patient's under-estimations at longer intervals, they speculated that the DLPFC was associated with time perception in a range beyond the working memory boundaries [8]. The DLPFC is engaged in both sustained attention and working memory [5] and is thought to be required to hold working memory for a longer period of time to achieve behavioral goals [9]. Therefore, a dysfunction of the DLPFC might cause interval timing errors as well as errors in daily life.

The MD nuclei [10] of the thalamus, especially parvicellular MD [2], are connected with the DLPFC, and SPECT of our patient revealed prefrontal hypoperfusion. Therefore, in the present case, the right MD nucleus lesion might have caused the DLPFC dysfunction and attentional and/or working memory deficits, leading to time disorientation and interval timing errors during the time production and estimation trials. Although thalamic chronotaraxis is reportedly associated with the left MD nucleus [2] or bilateral MD nuclei [1], those previously reported cases showed more severe symptoms of time disorientation than our case and cases of time disorientation involving a right thalamic lesion may have gone unrecognized due to milder and transient features. Moreover, since the right prefrontal cortex is considered to be associated with duration estimation (explicit timing) in the supra-second range [5], time judgement trials might have disclosed subclinical disturbances of time perception in our case. Thalamic chronotaraxis is transient and sometimes trivial, as in our patient, and further studies on cases exhibiting this phenomenon are warranted.

Conflict of interest

The authors have no conflicts of interest to report.

Author contributions

Ryuichiro Hayashi played a role in the acquisition, analysis, and interpretation of the data.

Yamaguchi Shigeki played a role in the enrollment of the subject and the acquisition of the data.

Katsumata Yasushi played a role in the analysis and interpretation of the radiological data.

Masaru Mimura played a role in the critical revision and supervision of the manuscript.